Therapeutic prostatic thermotherapy

ABSTRACT

The present invention provides a method of treating a prostate in a patient in need thereof and a heating catheter, or an electromagnetic radiation applicator, system suitable for effecting the present inventive method. The present inventive method provides for substantial unexpected improvement in patient outcome by providing, inter alia, a preferred therapeutic temperature for thermotherapy of the prostate and a method of decreasing a patient&#39;s intolerance due to pain. The present inventive system provides for, inter alia, automatic implementation of the present inventive method.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of copending application Ser.No. 60/084,714, filed May 8, 1998.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to the heat treatment of prostatedisorders, including, but not limited to, benign prostatic hyperplasia,prostatitis, and prostatic malignancy.

BACKGROUND OF THE INVENTION

Use of heating or energy radiating devices, particularly microwaveradiating devices, to administer heat for the treatment of variousdiseases of the prostate have been demonstrated to provide efficacioustreatment of various prostate conditions (Devonec et al., Monographs inUrology, 13, 77-95 (1992); De La Rosette et al., J. Urology, 157,430-438 (1997); Devonec et al., J. Endourology, 5, 129-135 (1991);Bernier et al., Curr. Opin. Urol., 7, 15-20 (1997)). Research hasindicated that the cellular transformations brought about by raisingtissue temperatures above certain levels can be used therapeutically. Attemperatures above 45° C., thermal damage has been found to occur tocells, even when the exposure to the elevated temperatures lasts foreven a short period of time. Thermal therapy has been defined as theprocess of heating tissue to greater than 45° C. to create necrosis.Both normal and abnormal cells respond to thermal exposure. Accordingly,therapies using heat have relied on healthy tissue regeneration afterthe delivery of a “thermal dose.” A thermal dose is a quantity which isindicative of the biological impact of elevated temperature maintainedfor a period of time. For the purposes of the present invention, thermaldosages can be calculated according to the method of Sapareto et al.,International Journal of Radiation Oncology, Biology, Physics, 10,787-800 (1984), except that the breakpoint of 45° C., rather than 43° C.is used for non-malignant tissues. That is, for the purposes of thepresent invention, thermal dose measured in Equivalent 45° C. hours isequal to the sum of the products of one-half of the treatmenttemperature in excess of 45° C. times the duration at that time, or${\sum\limits_{t = 0}^{t = {final}}\quad {0.5^{({45 - T})}\Delta \quad t}},$

wherein T is temperature in degrees centigrade and t is time in hours.

A variety of different methods have been developed to delivertherapeutically effective quantities of heat to the prostate, includingultrasound delivery devices, RF delivery devices and hotwater-recirculating catheters. One such device is the “WITT” hot waterrecirculating catheter, which is manufactured by ArgoMed, Inc. ofParsippany, New Jersey (USA). Another such device is the “Thermex II”,which is manufactured by Direx Systems, Ltd. While hot waterrecirculating catheters are useful in the context of the presentinvention, a significant drawback is that it is difficult to apply anaccurate thermal dose to the prostatic urethra while simultaneouslyavoiding delivery of a therapeutic dose of heat to non-target tissuessuch as the penis. Moreover, the design of hot water recirculatingcatheters can make accurate placement of the heating zones within thepatient more difficult. A limitation to the usage of RF applicators istheir relatively poor ability to penetrate tissue, often resulting insuperficial treatment of the prostatic tissue.

A more preferred method to deliver thermotherapy in the context of thepresent invention is via a urethrally-inserted catheter with an imbeddedmicrowave antenna. A cooling device is typically incorporated intomicrowave emitting catheters so that urethral tissue proximal to themicrowave antenna is cooled. The addition of this feature has beendirected at preserving the prostatic urethra, thereby reducing treatmentdiscomfort and post-treatment recovery time. A temperature or energymeasurement device can be used during treatments so that a thermal dosecan be measured. Treatments utilizing this approach includeTransUrethral Microwave Thermotherapy (TUMT). One disease currentlytreated by TUMT is Benign Prostatic Hyperplasia (BPH). The therapeuticeffect of such therapies can be measured in any suitable manner. Forexample, therapy can be measured by an improvement in the AUA symptomscore, or by an improvement in the Madsen-Iversen score, an improvementin urine flow, an improvement in urethral diameter, or the like.

The objective of TUMT of BPH is to destroy a portion of the prostatictissue, while preserving the tissue immediately adjacent to theprostatic urethra and the tissue immediately adjacent to the same.Current opinion in the field is that the greater the tissue destructionin the prostate, the more beneficial the treatment (De La Rosette etal., supra). Therefore, current device and therapy design is directed atimproving the maximum heat dose over the shortest period of time. Inthat regard, typical maximum temperatures frequently reach 65° C. orgreater within the prostate. Unfortunately, this has a number ofundesirable side-effects. For example, with prior art TUMT methods,hematuria rates typically exceed 30%, rates of urinary retentionrequiring long term catheterization usually exceeds 20%, rates ofurethral bleeding not merely due to catheterization exceed 5%, and ratesof urinary tract infection, ejaculatory disturbances, inflammation inthe urethra, chronic incontinence, and impotence are all statisticallysignificant and exceed about 1.5%.

There are, however, other delivery methods which utilize non-cooledradiation applicators and require the delivery of multiple treatments atrelatively low temperatures (45° C.-47° C. and lower). The objective ofthese methods is to obtain a therapeutic benefit while avoidingtemperature ranges that are commonly thought to cause patientintolerance and give rise to significant side effects. The problem withthese methods is that the data suggest, and current published opinion inthe art states, that efficacy is reduced. In addition, multipletreatment sessions are required at these relatively low temperatureswhich is inconvenient and uncomfortable for the patient and economicallydisadvantageous for the physician.

One significant drawback to other TUMT devices and therapies is thatthey are frequently painful for the patient and require the use ofnarcotic analgesics to control pain. This makes current TUMTinconvenient, limits the use of the therapy, adds to the expense andrecovery time, and can potentially result in patient loss.

A further drawback to other TUMT devices is the requirement for multipletreatment sessions and its limited efficacy. Thus, the economics of thetreatment are severely limited.

The electromagnetic radiation applicator systems developed for thetreatment of BPH have limited the ability of the skilled artisan tocontrol urethral and prostate temperatures. Many prior art radiationapplicator devices have controlled the heating of the prostate by simplycontrolling the power supplied to the heating unit. This method ofcontrolling the heating is typically necessary when the catheter systemis used in conjunction with a surface cooling device, because thesurface cooling device alters measured temperatures. Non-cooled cathetersystems (see, e.g., U.S. Pat. No. 4,967,765 to Turner et al.) have theability to monitor surface temperatures more accurately than cooledcatheter systems. However, these devices have also been constructed in amanner to limit complexity and cost. Accordingly, prior art cathetersystems have been capable of heating tissue to a pre-selectedtemperature and maintaining the tissue at that temperature, but have notincorporated the more advanced features of the present invention. Othercatheter designs useful in the context of the present inventive systemhave been commercially developed, e.g., by EDAP/Technomed and Urologix.While these other catheter designs are well known in the art, otherexamples are disclosed, e.g., by U.S. Pat. Nos. 4,620,480 and 5,628,770.

In view of the foregoing problems, there is a need for prostaticthermotherapy, particularly for BPH that is cost-effective, eliminatesthe use of general anesthesia and obviates the need for a cooledcatheter. There is also a need for a prostatic thermotherapy thatreduces non-beneficial side effects of previous methods.

The present invention provides such a method and related devices. Theseand other advantages of the present invention, as well as additionalinventive features, will be apparent from the description of theinvention provided herein.

BRIEF SUMMARY OF THE INVENTION

The present invention provides a method of heat treating a patient'sprostate tissue and devices, programs, and systems useful in practicingthe present inventive method.

Surprisingly, it has now been found that the maximum urethraltemperature that can be tolerated by patients to whom narcoticanalgesics or general anesthesia have not been administered exceeds thepreviously art-accepted maximum of 45° C.-47° C., under selectedconditions. It has also now been found that the side-effects which havebeen reported to accompany high temperature treatment of the prostateare substantially reduced by use of the method of the present inventionwhen the maximum urethral temperature is kept below about 57° C.Moreover, it has been surprisingly discovered that preservation of theprostatic urethra is not an important parameter of the thermotherapy ofthe prostate. On the contrary, the urethra and the urethrally proximalportions of the prostate are the tissues in which heating is desired inthe present inventive method. Thus, the present invention provides amethod of heat treating a patient's prostate tissue wherein thetemperature of the prostate tissue is raised from an initial temperaturebelow the destination temperature, to a destination temperature in therange of from 49° C. to almost 57° C. The destination temperature ismaintained for a period of time sufficient to administer a sufficientamount of heat to achieve a therapeutic effect on the prostate.

It has now been found that by allowing a patient to acclimatize toelevated urethral temperatures the patient's threshold of pain, with orwithout antiinflammatory analgesics, is elevated to about 60° C. Thus,the present invention provides a method of prostatic thermotherapywherein the maximum urethral temperature is raised to an elevatedtemperature which exceeds the previous art-accepted maximum by elevatingthe method temperature in such a manner so as to allow the patient toacclimatize the temperature elevation procedure. The rate at which thetemperature can be raised from 37° C. to the range of about 42° C. and46° C. can be relatively rapid. In keeping with the inventive method, itis desirable for the rate at which temperature is elevated from about44° C. to the destination temperature to occur more slowly. Further, therate of rise in temperature preferably decreases as the maximum urethraltemperature approaches the destination temperature. In general, the rateof increase in temperature according to the present invention variesbetween 1° C. per 0.5 minutes to 1° C. per 15 minutes. In order to allowbetter patient acclimatization, the rate of change in the temperaturepreferably does not exceed 5 1° C. per minute, and more preferably doesnot exceed 1° C. per 2 minutes. However, it is desirable to physicianand patient to minimize the amount of time required for therapy. Inorder to reduce the amount of time required to acclimate the patient toelevated urethral temperatures, the rate of temperature rise can beincreased to 1° C. per 10 minutes near the destination temperature andto about 1° C. per 2 minutes at the lower temperatures. The total timeto raise the urethral temperatures from 37° C. to the destinationtemperature preferably ranges from 15 minutes to 2 hours, and morepreferably is from 20 to 45 minutes. Moreover, it will be appreciatedthat the temperature rise can be continuous or discontinuous (i.e.,“stepped”).

The invention can best be understood with reference to the accompanyingdrawings and in the following detailed description of the preferredembodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of a urethral insertable electromagneticradiation applicator system according to an embodiment of the presentinvention.

FIG. 2 is a block diagram of the temperature control system and themicrowave applicator of the system illustrated in FIG. 1.

FIG. 3 is a flow chart of a temperature control program for regulatingthe temperature of body tissue heated by the microwave applicator ofFIG. 2.

FIG. 4 is a block diagram of a urethral insertable applicator systemsuitable for carrying out the present inventive method.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides a method of heat treating a patient'sprostate tissue and devices, programs, and systems useful in practicingthe present inventive method.

Surprisingly, it has now been found that the maximum urethraltemperature that can be tolerated by patients to whom narcoticanalgesics or general anesthesia have not been administered exceeds thepreviously art-accepted maximum of 45° C.-47° C., under selectedconditions. It has also now been found that the side-effects which havebeen reported to accompany high temperature treatment of the prostateare substantially reduced by use of the method of the present inventionwhen the temperature is kept below about 57° C. Moreover, it has beensurprisingly discovered that preservation of the prostatic urethra isnot an important parameter of the thermotherapy of the prostate. On thecontrary, the urethra and the urethrally proximal portions of theprostate are the tissues in which heating is desired in the presentinventive method. Thus, the present invention provides a method of heattreating a patient's prostate tissue wherein the temperature of theprostate tissue is raised from an initial temperature below thedestination temperature, to a destination temperature in the range offrom 49° C. to almost 57° C. The destination temperature is maintainedfor a period of time sufficient to administer a sufficient amount ofheat to achieve a therapeutic effort on the prostate.

It has now been found that by allowing a patient to acclimatize toelevated urethral temperatures the patient's threshold of pain, with orwithout antiinflammatory analgesics, is elevated to about 60° C. Thus,the present invention provides a method of prostatic thermotherapywherein the maximum urethral temperature is raised to an elevatedtemperature which exceeds the previous art-accepted maximum by elevatingthe method temperature in such a manner so as to allow the patient toacclimatize the temperature elevation procedure. The rate at which thetemperature can be raised from 37° C. to the range of about 42° C. and46° C. can be relatively rapid. In keeping with the inventive method, itis desirable for the rate at which temperature is elevated from about44° C. to the destination temperature to occur more slowly. Further, therate of rise in temperature preferably decreases as the maximum urethraltemperature approaches the destination temperature. In general, the rateof increase in temperature according to the present invention variesbetween 1° C. per 0.5 minutes to 1° C. per 15 minutes. In order to allowbetter patient acclimatization, the rate of change in the temperaturepreferably does not exceed 1° C. per minute, and more preferably doesnot exceed 1° C. per 2 minutes. However, it is desirable to physicianand patient to minimize the amount of time required for therapy. Inorder to reduce the amount of time required to acclimate the patient toelevated urethral temperatures, the rate of temperature rise can beincreased to 1° C. per 10 minutes near the destination temperature andto about 1° C. per 2 minutes at the lower temperatures. The total timeto raise the urethral temperatures from 37° C. to the destinationtemperature preferably ranges from 15 minutes to 2 hours, and morepreferably is from 20 to 45 minutes. Moreover, it will be appreciatedthat the temperature rise can be continuous or discontinuous (i.e.,“stepped”).

The total amount of heat delivered to the patient is also an importantparameter of the present inventive method. While patients are able toacclimate to temperatures up to about 60° C. if the rate of tissuetemperature increase is controlled, it is desirable to control the totalamount of heat administered to ensure both effective therapy andminimization of side effects. The administration of heat can bequantified by any suitable measurement, however, it is preferable toapproximate the quantity of heat administered using the method ofSapareto et al., International Journal of Radiation Oncology, Biology,Physics, 10, 787-800 (1984), modified such that the breakpoint of 45°C., rather than 43° C. is used for non-malignant tissues. Thus, while itis only an approximation of the actual thermal dose administered, forthe purpose of the present invention, thermal dose measured inequivalent 45° C. hours (or equivalent 45° C. minutes) is equal to thesum of the products of one-half raised to the result of 45 minus thetreatment temperature times the duration of time at that temperature, or${\sum\limits_{t = 0}^{t = {final}}\quad {0.5^{({45 - T})}\Delta \quad t}},$

wherein T is temperature in degrees centigrade and t is time in hours(or minutes). For purpose of the present invention, the contribution oftemperatures to the thermal dose below 45° C. can be ignored.

Table 1, below, illustrates several heating protocols, (utilized afterheating to about 44° C.) that are suitable in the context of the presentinvention. Each protocol is identified by a letter, A through H.Protocol A defines one preferred embodiment. Protocols B and C defineembodiments in which the destination temperature is held for a shorterperiods of time, while in the embodiment of protocols D and E the finaldestination temperature is held for a longer period of time (relative toprotocol A). Protocol F defines an embodiment in which the destinationtemperature is the lowest amongst the illustrated embodiments. ProtocolG defines an embodiment in which the destination temperature is higherthan the destination temperature of Protocols A-F. Protocol H, which isan operable, but not preferred embodiment of the present invention,illustrates that it is difficult to achieve both pain tolerance (throughthe use of tolerable rates of temperature increase) and to avoiddelivering a thermal dose in excess of about 30,000 equivalent 45° C.minutes (about 500 equivalent 45° C. hours). This is because 1 minute at60° C. is equivalent to 16,384 equivalent 45° C. minutes, withoutcalculating any temperature ramp time between body temperature and 60°C.

TABLE 1 Measured Urethral Temperature in Time at Measured CelsiusTemperature in Minutes Protocol: A B C D E F G H 44.0 1-2 1-2 1-2 1-21-2 1-2 1-2 1-2 45.0 1 1 1 1 1 1 1 1 45.5 1 1 1 1 1 1 1 1 46.0 2 2 2 2 22 1 1 46.5 1 1 1 1 1 1 1 1 47.0 2 2 2 2 2 2 2 2 47.5 2 2 2 2 2 2 2 248.0 2 2 2 2 2 2 2 2 48.5 2 2 2 2 2 2 2 2 49.0 3 3 3 3 3 100 3 3 49.5 22 2 2 2 2 2 50.0 3 3 3 3 3 3 3 50.5 2 2 2 2 2 2 2 51.0 45 20 30 75 90 33 51.5 3 3 52.0 3 3 52.5 3 3 53.0 4 4 53.5 3 3 54.0 4 4 54.5 3 3 55.0 44 55.5 4 4 56.0 4 56.5 . 5 57.0 . 4 57.5 4 58.0 5 58.5 4 59.0 5 59.5 460.0 5 Approximate Thermal 54 27 38 86 102 28 300 4160 Dose (eqv. 45° C.hrs.): Approximate Thermal 3230 1630 2270 5150 6110 1670 40600 249,600Dose (eqv. 45° C. min.):

Preferably, the gradual increase in temperature is automaticallyregulated. Accordingly, for electromagnetic radiating catheters, it ispreferable for the power source that provides the energy to theradiation applicator be in operable association with urethraltemperature sensors by way of a microprocessor, computer, or the like.Similarly, for heating catheters (e.g., hot water heaters) it ispreferable for an automatic regulator to control the temperature of thecatheter positioned in the prostatic urethra.

The present invention also provides a surprisingly effective form ofthermotherapy of the prostate. Prior art methods have called for maximumtreatment temperatures at about 47° C. or lower (“low temperaturetreatments”) or at temperatures well in excess of 60° C. (“hightemperature treatments”). However, thermotherapy according to thepresent invention is advantageously conducted at a temperature of from49° C. to about 57° C., and preferably, at a temperature of from about50° C. to about 55°C. It will be appreciated that in a prostate in whichthe tissue temperature sensor measures a temperature of 51° C. to 52° C.that the actual range of temperatures in the heated tissue will vary andin isolated places can reach temperatures as high as 55° C. Tissuetemperature variation is consequence of uneven dispersion of energy fromthe antenna or heating portion of the catheter, differential absorptionof the dispersed energy by the targeted tissue, and variations in bloodperfusion through the target tissue. Blood, of course, will be about 37°C. in a human and acts as coolant. Preferably patient tissue is heatedto a maximum average sensed temperature of about 51° C. to about 52° C.

Thermotherapy conducted in this temperature range is more effective thanthat conducted at the lower temperature ranges and is not accompanied byan increase in side-effects (except for the need to anesthetize thepatient with medication or acclimate the patient by gradually increasingurethral temperatures). Moreover, thermotherapy of the prostateperformed in accordance with the present invention is accompanied bysubstantially fewer side effects such as, for example, hematuria,dysuria, tissue slough, retrograde ejaculation, extended catheterizationand the like; see De La Rosette et al., supra than thermotherapyperformed at temperatures exceeding 60° C .

The temperature of the prostate is maintained at the destinationtemperature (regardless of whether the temperature is gradually orrapidly increased to the destination temperature) for a period of timesuitable to effect a therapeutic result (e.g., a decrease in the AUAsymptom score). Suitable times at the treatment temperature can be asshort as about 0.5 minutes, but are preferably at least 30 minutes.Suitable times at the treatment temperature can be as long as desired,but in order to avoid overdosage of heat, undesirable side-effects, andloss of time, the time at the treatment temperature can be as long asabout 4 hours, but preferably is not longer than about 2 hours, and morepreferably is not longer than about 1 hour. Treatment time should takeinto account the thermal dose that is administered.

Heat treatment according to the present invention preferably providesthe urethra proximal tissues with a heat dose that is sufficient toprovide a therapeutic effect, but which is low enough to avoid excessiveundesired side-effects. For example, treatment according to the presentinvention provides at least an estimated minimum cumulative thermal doseof at least about 1500 equivalent 45° C. minutes (i.e., 25 equivalent45° C. hrs.). More preferably, treatment according to the presentinvention provides at least about 2000 equivalent 45° C. minutes.Treatment according to the present invention preferably provides anestimated maximum cumulative thermal dose which does not exceed about30,000 equivalent 45° C. minutes, and more preferably does not exceedabout 20,000 equivalent 45° C. minutes, and yet more preferably does notexceed about 7000 equivalent 45° C. minutes.

The present inventive method is specifically designed to provide thehighest temperatures in the prostatic urethra consistent with minimizingside effects and patient discomfort. The method is preferablyaccomplished in a straightforward method by not using a cooled catheter.A cooled catheter causes the peak temperatures to occur a well withinthe prostate away from the urethral walls. When a cooled catheter isused, measured tissue temperatures decline rapidly as the urethra isapproached, such that the 2 mm of prostate tissue proximal to theurethra typically do not receive therapeutic quantities of heat.However, rather than attempting to insulate these tissues, the presentinvention seeks to directly treat these tissues. When a heating catheteror non-cooled electromagnetic-radiating catheter is used the highesttemperatures are reached in the urethra. Temperature declines deeperinto the prostate tissue away from the catheter. Surprisingly, thisheating pattern provides substantially more effective treatment.

Moreover, high temperature prior art techniques have focused on ablationof deep prostate tissue with the idea that eliminating deep prostatictissue mass would decrease the pressure on the urethra allowing betterurine flow and other benefits. In contrast, the present inventive methoddoes not have the goal of decreasing prostate volume or mass andsubstantial changes in prostate volume or mass are not an expectedoutcome of the present inventive therapy. While applicants do not wishto be bound to any particular theory, it is believed that theapplication of an appropriate dose of heat to the prostatic urethra andthe urethrally proximal prostate tissue causes a change in sensation. Itis not known whether this change in sensation is accompanied by physicalchanges to the nerve bundles extending along the urethra through theprostate, but it is conceivable that these neurons are the true targetsof the thermotherapy. In any event, while it is possible to use acatheter with a cooling device to practice the present invention, thereis not a compelling medical reason to do so.

By limiting all tissue temperatures to less than about 57° C., andpreferably less than about 55° C., the substantial side-effectsaccompanying very high temperature thermal therapy are advantageouslyavoided. Treatment according to the present invention is not unduly orintolerably painful. However, pain relieving medication can beoptionally administered. Preferably, treatment according to the presentinvention does not require narcotic analgesics, however, the use ofantiinflammatory analgesics and mild anxiolytics can be administeredaccording to the judgement of the skilled clinician.

The present inventive method can be carried out by any suitable device,FIG. 4 provides a block diagram of a urethrally insertable heatingapplicator system sutibale for implementing the present invention. Anexample of the device illustrated in FIG. 4 is provided below in FIG. 1.The system includes a catheter 14 for insertion into the urethra. Thecatheter 14 generally encloses an applicator (or fluid) 15 capable ofpassing energy through the wall of the catheter to body tissue,particularly a prostate gland undergoing treatment. The enery applicatormay be of any suitable design as described elsewhere herein, including,a design employing an ultrasound delivery device, an RF delivery device,a hot water-recirculating chamber, and more preferably, a microvaveapplicator. The system includes a temperature control system 16 forregulating the temperature of the tissue heated by the energy applicator15.

One aspect of the present invention provides a urethral insertableelectromagnetic radiation applicator system suitable for implementingthe present inventive method. FIG. 1 provides a block diagram of anexample of a urethral insertable electromagnetic radiation applicatorsystem according to an embodiment of the present invention. The systemincludes a catheter 1 for insertion into the urethra. The catheter 1generally is adapted to enclose a microwave applicator 2. As illustratedin FIG. 2, the microwave applicator includes an antenna 10 for radiatingelectromagnetic energy through the wall of the catheter to body tissue,particularly a prostate gland undergoing treatment.

In this embodiment, the catheter 1 and the microwave applicator 2 may bevariously configured, and can be similar to the catheter and theapplicator disclosed in U.S. Pat. No. 4,967,765, the disclosure of whichis hereby incorporated by reference in its entirety. In the referenceddocument, the microwave applicator includes a helical coil antennamounted inside a urethral catheter. A suitable electrical connector,such as a coaxial cable connects the antenna to external excitationelectronics. The antenna delivers electromagnetic radiation through thewall of the catheter to heat tissue adjacent to the catheter. Using ahelical coil antenna is preferred to provide substantially uniformheating along the length of the antenna.

According to an important aspect of the invention, the applicator systemincludes a temperature control system 3 for regulating the temperatureof tissue heated by the microwave applicator 2. Although the temperaturecontrol system may be an open loop system or a closed loop system, in apreferred embodiment, the temperature control system 3 comprises aclosed loop system. In a most preferred embodiment, the temperaturecontrol system senses the temperature of tissue to being heated by themicrowave applicator and regulates the electromagnetic energy output bythe microwave applicator based on the sensed tissue temperature.Regulating the electromagnetic energy output by the microwave applicatorbased on the sensed tissue-temperature is preferred, because the tissuetemperature may be a non-linear function of applied electromagneticenergy. More particularly, when electromagnetic energy is applied totissue, such as the tissue of the prostate gland, the resultingtemperature of the tissue depends on a variety of factors, for example,the blood flow to the tissue. Moreover, the relationship betweentemperature and applied electromagnetic energy may vary from one patientto the next. In conventional systems, the power applied to microwaveapplicators was simply increased in fixed power increments. For example,the power was increased by x watts every y minutes. Such a system isless preferred because of the variable relationship between appliedelectromagnetic energy and tissue temperature. Thus, by controlling theapplied electromagnetic energy based on an accurately sensedtemperature, embodiment of the present invention are capable ofaccurately regulating tissue temperature, while accounting forvariations in the tissue being heated.

FIG. 2 illustrates an example of a block diagram of the temperaturecontrol system 3 and the microwave applicator 2 according a preferredembodiment of the invention. In the illustrated embodiment, thetemperature control system 3 comprises a temperature sensor 4 capable ofsensing tissue temperature, signal conditioning circuitry 5 forconditioning the output signal from the temperature sensor 4, amicrocontroller 6 for producing a temperature control signal based onthe output signal from the temperature sensor 4, and an electromagneticenergy source 8 for applying electromagnetic energy to the antenna 10.The components illustrated in FIG. 2 cooperate to control thetemperature of tissue being treated in response to the sensed tissuetemperature.

The temperature sensor 4 may be variously configured. For example, thetemperature sensor 4 may comprise a thermistor or thermocouple capableof sensing the temperature of tissue, such as the tissue of the prostategland. In an alternative embodiment, the temperature sensor 4 maycomprise a resistance temperature difference (RTD) sensor. Thetemperature sensor 4 preferably produces an output signal, e.g., avoltage, indicative of the tissue temperature.

The signal conditioning circuitry preferably receives the output signalfrom the temperature sensor and conditions the signal for processing bythe microcontroller 6. For example, the signal conditioning circuitrymay include a low-pass filter for filtering noise from the signal fromthe temperature sensor 4. The signal conditioning circuitry may alsoinclude an amplifier, such as an operational amplifier, for amplifyingthe signal output from the temperature sensor 4. The gain of theoperational amplifier is preferably selected so that the voltage rangeof the output signal of the signal conditioning circuitry matches theinput voltage range of the microcontroller 6.

The microcontroller 6 may be variously configured. For example, themicrocontroller 6 may comprise a microprocessor including internalmemory circuits and analog to digital conversion circuitry, forprocessing the output signal from the signal conditioning circuitry andproducing the temperature control signal. Although the illustratedembodiment depicts a microcontroller having an internal analog todigital converter, the present invention is not limited to such anembodiment. For example, the analog to digital converter may be externalto the microcontroller 6. A temperature control program controls themicrocontroller to output the temperature control signal based on thesensed tissue temperature. The temperature control program may be storedin memory internally or externally to the microcontroller. In analternative embodiment, the temperature control program may be stored ina portable computer-readable storage medium, such as a magnetic disk oran optical disk. Utilizing a temperature control program to produce thecontrol signal is preferred because the program can be updated astreatment protocols, e.g., treatment temperatures and/or durations,change.

The present invention is not limited to utilizing a microcontroller 6 toproduce the temperature control signal. For example, analog or digitalcircuitry that performs equivalent functions to the microcontroller orthe temperature control program is within the scope of the invention.

An electromagnetic energy source 8 receives the temperature controlsignal from the microcontroller and applies electromagnetic energy tothe antenna. In a preferred embodiment, the electromagnetic energysource comprises an oscillator. The frequency of oscillation of theoscillator is preferably selected for optimal heating of tissue withinFCC regulations. The oscillation frequency of the electromagnetic energysource is preferably selected to be about 915 MHz or about 12, inaccordance with present FCC regulations. However, the present inventionis not limited an oscillation frequency of 915 MHz. For example, ifanother frequency is determined to be more therapeutically beneficialand/or FCC regulations change, the preferred frequency of oscillationmay change accordingly.

The antenna 10 receives the electromagnetic energy from the source 8 andradiates the energy to the tissue being treated. As stated above, theantenna preferably comprises a helical coil antenna. However, thepresent invention is not limited to helical coil antennas. Any antennathat produces a substantially uniform radiation pattern over a desiredarea of treatment is within the scope of the invention.

FIG. 3 is a flow chart of an example of a temperature control programaccording to an embodiment of the present invention. Once the catheter 1is inserted into the urethra and the antenna is positioned near theprostate gland, the electromagnetic energy source is actuated. In orderto avoid having to anesthetize the patient, the program preferablyincreases the temperature in predetermined or specified increments andmaintains the temperature at each increment for a predetermined orspecified duration. The temperature control program may store orcalculate a plurality of desired prostatic tissue temperatures and atreatment duration corresponding to each temperature. The temperaturesensor measures the tissue temperature. The control program may samplethe measured temperature and store the measured temperature in memory.The program determines whether a first desired temperature level fortreatment has been reached, i.e., by comparing the measured temperaturestored in memory to one of desired treatment temperatures. If the firsttemperature has not been reached, the microcontroller continuesincreasing the temperature. Once the first temperature has been reached,the microcontroller adjusts the temperature control signal to maintainthe first temperature. In order to maintain the first temperature, themicrocontroller adjusts the temperature control signal based on theoutput signal from the temperature sensor, i.e., by sampling andcomparing the measured temperature to the first desired temperature.

According to a preferred embodiment, the microcontroller also measuresand controls the duration of treatment at each desired temperature. Thismeasurement may be performed by executing a timer routine once eachdesired temperature is reached. The timer routine records the durationof the treatment at each desired temperature. The program compares therecorded duration to a desired duration. Once the desired duration hasbeen reached, the program continues to the next processing step. In analternative embodiment, an external timer circuit may be coupled to themicrocontroller to measure treatment duration.

Once treatment occurs at a first desired temperature for a first desiredtime period, the control program determines whether the firsttemperature is the final or destination temperature in the processingroutine. If the first temperature is the final or destinationtemperature, the program deactuates the electromagnetic energy sourceand ends. However, because the treatment preferably occurs at aplurality of different temperature levels, the temperature controlprogram preferably increases the power level after the treatment at thefirst temperature so that treatment can occur at a second at a secondtemperature, preferably higher than the first temperature. The controlprogram preferably repeats these steps, i.e., increasing the temperatureuntil a desired temperature is reached, maintaining the temperature atthe desired temperature for a desired duration, then increasing thetemperature to the next level. Because the power level is controlledbased on the sensed tissue temperature, the control programautomatically tailors itself to each patient.

As stated above, the control program preferably steps through aplurality of temperature levels with predetermined or specifieddurations. The predetermined or specified durations may be fixed orvariable. The number of levels, the temperature at each level, and theduration of each level are preferably selected to reduce patientdiscomfort and increase the effectiveness of treatment. In a mostpreferred embodiment, the temperature levels and durations are selectedas shown in Table 1 above.

As illustrated in Table 1, a preferred embodiment of the treatmentprotocol begins at 44° C. In order to reach a tissue temperature of 44°C., the control program may actuate the electromagnetic source at aninitial level until 44° C. is reached. The program may increase thetemperature in predetermined or specified steps, as illustrated in FIG.3 in order to reach 44° C. In an alternative embodiment, since the lowtemperature portion, e.g., between about 37° C. and about 440° C., ofthe treatment protocol is not as important, the control program mayactuate the electromagnetic energy source such that the antenna deliversone watt during each 30 second time internal until 44° C. is reached.Once 44° C. is reached, the temperature control program preferablycontrols the energy applied by the antenna based on the sensed tissuetemperature as illustrated in Table 1. For example, when the tissuetemperature measured by the temperature sensor is 44° C., themicrocontroller executes a timer routine. When the timer routine reaches1 minute, the microcontroller preferably increases the power applied bythe electromagnetic energy source to increase the tissue temperature tothe next level, e.g., 44.5° C. When the tissue temperature measured bythe temperature sensor reaches 44.5° C., the microcontroller preferablymaintains that level and re-executes the timer routine. In this manner,the microcontroller and the temperature sensor step through the desiredtreatment protocol. Because the temperature increments according toTable 1 are relatively small, e.g., about 0.5 degrees, the patient isable to acclimate to the elevated temperatures, discomfort is minimized,and the need for narcotic analgesics and/or general anesthesia isattenuated or eliminated.

Once the destination temperature is reached and maintained for a desiredtime period, the control program deactuates the electromagnetic energysource and ends. According to Table 1, the destination temperature ispreferably 51° C. and the treatment duration at that temperature is 45minutes. However, the present invention is not limited to a destinationtemperature of 51° for a duration of 45 minutes. For example, thedestination temperature is preferably between 49° C. and about 57° C.,and more preferably between about 50° C. and about 55° C. Also, theaverage maximum sensed temperature is between about 51° C. and about 52°C. The treatment duration at the destination temperature preferably doesnot exceed about 60 minutes.

The present invention is not limited to the temperature below thedestination temperature or the durations at these temperaturesillustrated in Table 1. For example, the control program may control thetissue temperatures such that the temperature is increased in incrementsof about 1° C. The treatment duration at each temperature is preferablyselected to range from no less than about 30 seconds to no more thanabout 15 minutes, and more preferably no less than about 1 minute to nomore than about 10 minutes, and even more preferably no less than about2 minutes to no more than about 5 minutes. The longer the duration ateach temperature, the lower the discomfort level of the patient. On theother hand, increasing the duration also increases treatment time. Thus,the upper limit of about 15 minutes per degree is preferably notexceeded.

Although increasing the temperature in predetermined or specified stepsis preferred, the present invention is not limited to such anembodiment. For example, the control program may implement a slowramping function from an initial temperature to a destinationtemperature. The initial temperature may be about 37° C. The destinationtemperature may be about 51° C. In order to implement the rampingfunction the temperature control program may actuate the electromagneticenergy source. The temperature sensor measures the tissue temperature.The temperature control program may sample and store valuescorresponding to the measured temperature. The control program maydetermine the rate of change of the temperature signal, i.e., bydifferentiating the temperature signal utilizing the stored values. Thecontrol program may compare the calculated rate of change to a desiredrate of change. If the rate of change in temperature is greater than thedesired rate of change, the temperature sensor decreases the energysupplied by the electromagnetic energy source. If the rate of change intemperature is less than the desired rate of change, the temperaturesensor decreases the power supplied by the electromagnetic energysource. If the rate of change is less than a desired rate of change, thetemperature control program increases the energy supplied byelectromagnetic energy source. The desired rate of increase intemperature may be fixed or variable. Once the destination temperatureis reached, the temperature control program preferably maintains thedestination temperature for a predetermined or specified time period, asdescribed above.

All of the references cited herein, including patents, patentapplications, and publications, are hereby incorporated in theirentireties by reference.

While this invention has been described with an emphasis upon preferredembodiments, it will be obvious to those of ordinary skill in the artthat variations of the preferred embodiments may be used and that it isintended that the invention may be practiced otherwise than asspecifically described herein. Accordingly, this invention includes allmodifications encompassed within the spirit and scope of the inventionas defined by the following claims.

What is claimed is:
 1. A method of treating a prostate for benignprostatic hyperplasia or prostatitis in a patient having a urethra,comprising elevating the temperature of the prostate to a destinationtemperature and for a time sufficient to achieve a therapeutic effect onthe prostate, the energy being applied with a catheter system comprisinga non-cooled catheter for insertion into the urethra, a heat applicatorattached to the catheter. and a connector for connecting the applicatorto an energy source, the method comprising a first heating step ofwarming tissue proximal to the applicator up to an initial temperature,the initial temperature being in the range of about 42° C. to about 46°C., followed by a second heating step, the second heating stepcomprising gradually increasing the temperature of the tissue proximalto the applicator to the destination temperature in the range of from49° C. to about 57° C. such that the mean rate of increase intemperature is from about 0.5 minute/° C. to about 15 minute/° C.
 2. Themethod of claim 1, wherein the mean rate of increase in temperature,during the second step, is from about 1.0 minute/° C. to about 10minute/° C.
 3. The method of claim 2, wherein the mean rate of increasein temperature, during the second step, is selected such that from about15 minutes to about 2 hours separate the time points when the tissuesurrounding the applicator rises from the initial temperature to thedestination temperature.
 4. The method of claim 3, wherein the mean rateof increase in temperature is selected such that from about 15 minutesto about 45 minutes separate the time points when the tissue surroundingthe applicator rises from the initial temperature to the destinationtemperature.
 5. The method of claim 1, wherein the second heating stepis controlled by a microcontroller, such that the second step occursindependent of direct human intervention after the initiation of thesecond step.
 6. The method of claim 1, wherein the method is tolerableto the patient such that it is not necessary to administer a narcoticanalgesic to the patient.
 7. A method of treating a prostate for benignprostatic hyperplasia or prostatitis in a patient comprising applyingenergy to the prostate to elevate the temperature of the prostate to atherapeutic temperature and for a time sufficient to achieve atherapeutic effect on the prostate, the energy being applied such thatthe temperature of the prostate tissue is raised from an initialtemperature of below the therapeutic temperature to a destinationtemperature in the range of from 49° C. to about 57° C., the methodfurther comprising a first heating step of warming the prostate up tocritical maximum temperature, the critical maximum temperature being inthe range of about 42° C. to about 46° C., followed by a second heatingstep, the second heating step comprising gradually increasing themaximum temperature of the prostate to the destination temperature suchthat the mean rate of increase in temperature is from about 0.5 minute/°C. to about 15 minute/° C.
 8. The method of claim 7, wherein the meanrate of increase in temperature, during the second step, is from about1.0 minute/° C. to about 10 minute/° C.
 9. The method of claim 8,wherein the method does not comprise the administration of a narcoticanalgesic to the patient.
 10. The method of claim 7, the method furthercomprising, applying energy to the prostate to elevate the temperatureof the prostate to a therapeutic temperature and for a time sufficientto achieve a therapeutic effect on the prostate, the energy beingapplied with a heated catheter system comprising a non-cooled catheterfor insertion into the urethra, a heat applicator attached to thecatheter, and a connector for connecting the applicator to a source ofenergy sufficient to elevate the temperature of tissue surrounding theapplicator to the therapeutic temperature and for maintaining thetherapeutic temperature for a time sufficient to effect therapy of theprostate, and the energy being applied such that a thermal dose of about1500 equivalent 45° C. minutes to about 30,000 equivalent 45° C. minutesis applied to the tissue surrounding the applicator.
 11. The method ofclaim 10, wherein a thermal dose of from about 2000 equivalent 45° C.minutes to about 30,000 equivalent 45° C. minutes is applied to thetissue surrounding the applicator.
 12. The method of claim 11, whereinthe heated catheter is a hot water recirculating catheter.
 13. Themethod of claim 11, wherein the source of energy is hot water.
 14. Themethod of claim 11, wherein the source of energy is microwave.
 15. Themethod of claim 11, wherein the source of energy is ultrasonic or RF.16. The method of claim 11, wherein the method comprises first heatingthe applicator to a temperature in the range of from about 42° C. toabout 46° C., followed by gradually increasing the temperature of theapplicator to the therapeutic temperature such that the mean rate ofincrease in temperature after the temperature range of about 42° C. toabout 46° C. has been achieved is from about 0.5 minute/° C. to about 15minute/° C.
 17. The method of claim 16, wherein the mean rate oftemperature increase after the temperature range of about 42° C. toabout 46° C. has been achieved is from about 1 minute/° C. to about 10minute/° C.
 18. The method of claim 16, wherein the mean rate oftemperature increase after the temperature range of about 42° C. toabout 46° C. has been achieved is from about 1 minute/° C. to about 10minute/° C.
 19. The method of claim 10, wherein a thermal dose of fromabout 1500 equivalent 45° C. minutes to about 20,000 equivalent 45° C.minutes is applied to the tissue surrounding the applicator.
 20. Themethod of claim 19, wherein the heated catheter is a hot waterrecirculating catheter.
 21. The method of claim 19, wherein the sourceof energy is hot water.
 22. The method of claim 19, wherein the sourceof energy is microwave.
 23. The method of claim 19, wherein the sourceof energy is ultrasonic or RF.
 24. The method of claim 19, wherein themethod comprises first heating the applicator to a temperature in therange of from about 42° C. to about 46° C., followed by graduallyincreasing the temperature of the applicator to the therapeutictemperature such that the mean rate of increase in temperature after thetemperature range of about 42° C. to about 46° C. has been achieved isfrom about 0.5 minute/° C. to about 15 minute/° C.
 25. The method ofclaim 10, wherein a thermal dose of from about 1500 equivalent 45° C.minutes to about 7000 equivalent 45° C. minutes is applied to the tissuesurrounding the applicator.
 26. The method of claim 25, wherein theheated catheter is a hot water recirculating catheter.
 27. The method ofclaim 25, wherein the source of energy is hot water.
 28. The method ofclaim 25, wherein the source of energy is microwave.
 29. The method ofclaim 25, wherein the source of energy is ultrasonic or RF.
 30. Themethod of claim 25, wherein the method comprises first heating theapplicator to a temperature in the range of from about 42° C. to about46° C., followed by gradually increasing the temperature of theapplicator to the therapeutic temperature such that the mean rate ofincrease in temperature after the temperature range of about 42° C. to46° C. has been achieved is from about 0.5 minute/° C. to about 15minute/° C.
 31. The method of claim 30, wherein the mean rate oftemperature increase after the temperature range of about 42° C. toabout 46° C. has been achieved is from about 1 minute/° C. to about 10minute/° C.
 32. The method of claim 10, wherein the heated catheter is ahot water recirculating catheter.
 33. The method of claim 10, whereinthe source of energy is hot water.
 34. The method of claim 10, whereinthe source of energy is microwave.
 35. The method of claim 10, whereinthe source of energy is ultrasonic or RF.
 36. A method of treating aprostate for benign prostatic hyperplasia or prostatitis in a patienthaving a prostate and a urethra comprising applying energy to theprostate to elevate the temperature of the prostate to a therapeutictemperature and for a time sufficient to achieve a therapeutic effect onthe prostate, the energy being applied with a heated catheter systemcomprising a non-cooled catheter for insertion into the urethra, a heatapplicator attached to the catheter, and a connector for connecting theapplicator to a source of energy sufficient to elevate the temperatureof tissue surrounding the applicator to the therapeutic temperature andfor maintaining the therapeutic temperature for a time sufficient toeffect therapy of the prostate, and, wherein the method furthercomprises first heating the applicator to a temperature in the range offrom about 42° C. to about 46° C., followed by gradually increasing thetemperature of the applicator to the therapeutic temperature such thatthe mean rate of increase in temperature after the temperature range ofabout 42° C. to about 46° C. has been achieved is from about 0.5minute/° C. to about 15 minute/° C. the energy being applied such that athermal dose of about 1500 equivalent 45° C. minutes to about 30,000equivalent 45° C. minutes is applied to the tissue surrounding theapplicator.
 37. The method of claim 36, wherein the mean rate oftemperature increase after the temperature range of about 42° C. toabout 46° C. has been achieved is from about 1 minute/° C. to about 10minute/° C.
 38. A method of treating a prostate for benign prostatichyperplasia or prostatitis in a patient having a prostate and a urethra,comprising applying energy to the prostate to elevate the temperature ofthe prostate to a therapeutic temperature and for a time sufficient toachieve a therapeutic effect on the prostate, the energy being appliedwith a heated catheter system comprising a non-cooled catheter forinsertion into the urethra, a heat applicator attached to the catheter,and a connector for connecting the applicator to a source of energysufficient to elevate the temperature of tissue surrounding theapplicator to the therapeutic temperature and for maintaining thetherapeutic temperature for a time sufficient to effect therapy of theprostate, and the energy being applied such that a thermal dose of about1500 equivalent 45° C. minutes to about 30,000 equivalent 45° C. minutesis applied to the tissue surrounding the applicator, wherein the tissuesurrounding the applicator is heated according to protocol A, B, C, D,E, F, or G set forth in Table
 1. 39. The method claim 38, wherein thetissue surrounding the applicator is heated according to protocol A, B,C, D, or E set forth in Table 1.